If you were to ask me what kind of a Mass Effect movie I'd make, I'd follow these basic principles.
1. No Shepard. It's not because I don't think Shepard is an interesting character, but mostly that I wouldn't want to tell folks who love playing the games that this is how Shepard should behave and act. Last thing I'd ever want to do is pull another "Revan is male and is light side in canon". Shepard should belong to the players.
2. That being said, this would also mean the story's characters will probably consist of entirely new characters if not all of them. I like the idea of characters doing important things in the universe that don't revolve around the main characters from the game. Gives the universe a sense of competence and awareness you don't normally see in other science fiction works. That's not to say that classic characters wouldn't appear, just that they wouldn't be treated as the thing that ends up saving the day for everyone.
3. So far things are sounding like Paragon Lost, but this is where it gets different. I'd Shoot for an alien lead. This is without a doubt the hardest thing to pull off and sell, but like point number 2, I'd like a Mass Effect story to be a lot more about the universe rather than another human story. There are plenty of human like elements and behaviors in almost every race in the game that people can identify and relate to.
4. Screw Earth. Screw Earth HARD. There's really no reason why BioWare had to fall back on it like they did in ME3 except to make a gimmicky story line that's been used more times than I care to count in other works of science fiction.
As you can probably summarize with all these points, my overall approach would be to focus on what makes the Mass Effect universe unique and dive right into it. No human lead or a human centered story line. Doesn't mean humans won't be involved or play a major role in the story, it just won't be a "humanity saves the day!" or "humans vs. aliens" story.
Oh, one other thing. If this is not going to be a side story in the game and we're free to move around a bit with the story,
5. There will be no Catalyst and there will be no Crucible. The true purpose behind the Reapers' cycle of genocide is going to be different and there will be no outside force that controls them. Their reasons will be their own so they will remain the threat. I've come up with some ideas on why they're doing the things they're doing, and I think in the hands of a good writer, it can work a lot better than what we got in ME3.
Again, the no human lead will probably kill this pitch the moment it's mentioned, but that is how I would approach making a Mass Effect movie.